The Impact of Human Immunodeficiency Virus Infection on Gut Microbiota α-Diversity: An Individual-level Meta-analysis

Background: Whether human immunodeficiency virus (HIV) infection impacts gut microbial α-diversity is controversial. We reanalyzed raw 16S ribosomal RNA (rRNA) gene sequences and metadata from published studies to examine α-diversity measures between HIV-uninfected (HIV^-) and HIV-infected (HIV⁺) individuals. Methods: We conducted a systematic review and individual level meta-analysis by searching Embase, Medline, and Scopus for original research studies (inception to 31 December 2017). Included studies reported 16S rRNA gene sequences of fecal samples from HIV⁺ patients. Raw sequence reads and metadata were obtained from public databases or from study authors. Raw reads were processed through standardized pipelines with use of a high-resolution taxonomic classifier. The χ² test, paired t tests, and generalized linear mixed models were used to relate α-diversity measures and clinical metadata. Results: Twenty-two studies were identified with 17 datasets available for analysis, yielding 1032 samples (311 HIV^-, 721 HIV⁺). HIV status was associated with a decrease in measures of α-diversity (P <. 001). However, in stratified analysis, HIV status was associated with decreased α-diversity only in women and in men who have sex with women (MSW) but not in men who have sex with men (MSM). In analyses limited to women and MSW, controlling for HIV status, women displayed increased α-diversity compared with MSW. Conclusions: Our study suggests that HIV status, sexual risk category, and gender impact gut microbial community α-diversity. Future studies should consider MSM status in gut microbiome analyses.